Background: Isotretinoin for oral therapy in severe acne conglobata and acne nodulocystica represents a significant achievement; however, the drug exerts several mucocutaneous and systemic adverse effects, besides its teratogenic potency. Objective: The aim of this study was to investigate the plasma levels of isotretinoin and of 4-oxo-isotretinoin over long-term treatment of severe acne and to assess any correlation with the given dose, the clinical improvement and the occurrence of side effects. Methods: Forty-one patients with severe acne and acne-related disorders were studied under long-term oral intake of isotretinoin. Therapeutic effects and side effects were evaluated prior, during and at the end of therapy. The plasma levels of isotretinoin and of its major metabolite 4-oxoisotretinoin were measured by reversed-phase HPLC and were correlated with the administered oral dose and the number and frequency of side effects. Results: Dose-dependent plasma levels of isotretinoin and its metabolite were observed. At a mean dosage of 0.75–1.0 mg/kg/day, 404 ± 142 ng/ml were measured, whereas the plasma levels of 4-oxo-isotretinoin were 1–2 × higher. The plasma levels correlated well with the orally administered dose of isotretinoin and the observed mucocutaneous side effects. Conclusion: The study demonstrates that measuring of the plasma levels may be a helpful tool to monitor the individual therapeutic dose regimen in patients with severe acne in order to minimize undesired side effects and to control oral intake.

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